Approach
Primary care physicians are generally on the front line of care for patients with diabetes-related foot disease. As such, most of the initial evaluation and management is done through primary care clinics.
Endocrinologists and other medical specialists may also be involved in the evaluation and management of these patients. An interprofessional approach facilitated by a podiatrist is recommended by the American Diabetes Association (ADA) for all patients with foot ulcers and high-risk feet.[22]
There are five key principles which form the mainstay of management of diabetic foot ulcers:[38]
Wound debridement
Wound dressings
Pressure offloading
Treatment of infection
Treatment of ischemia and restoration of tissue perfusion
The majority of foot ulcers will heal provided treatment is based on these principles, according to guidelines from the International Working Group on the Diabetic Foot (IWGDF).[38] They also emphasize the importance of holistic, person-centered care that goes beyond the feet, to include: optimizing glycemic control and cardiovascular risk factors, treating edema, malnutrition and depression, and addressing other psycho-social difficulties.[38]
The three key factors associated with limb loss include degree of tissue loss (wound severity), severity of ischemia, and severity of foot infection.[53]
It is important to remember the need for proper management of the diabetes itself (e.g., regular check-ups, maintenance of target blood glucose levels, blood pressure, and lipid management) according to current guidelines. These goals do not change in the presence or absence of diabetes-related foot disease. There is some evidence that intensive glucose control is associated with a long-term reduction in risk of developing diabetic foot ulcers in patients with type 1 diabetes.[60]
Sodium-glucose cotransporter-2 (SGLT2) inhibitors should not be started in drug-naïve people with a diabetes-related foot ulcer or gangrene, and temporary discontinuation should be considered in people who develop a foot ulcer or gangrene while already using them, until the foot is healed, according to joint guidelines from the IWGDF, European Society for Vascular Surgery (ESVS) and Society for Vascular Surgery (SVS).[10] This is due to a rare but serious side effect of diabetic ketoacidosis (DKA) with SGLT2 inhibitors, which is made more likely during acute illness and perioperative periods. As patients with peripheral arterial disease, foot ulcers or gangrene are vulnerable to infections and may need to undergo urgent surgery, it is therefore pragmatic to avoid these drugs to reduce DKA risk. Moreover, canagliflozin was associated with an increased risk of amputation in one randomized controlled trial.[61] Although this finding has not been borne out by other studies, the IWGDF/ESVS/SVS guidelines note that people with foot ulcers were frequently excluded from clinical trials of SGLT2 inhibitors so their safety in these patients remains uncertain.[10]
For more information on the medical management of diabetes in general, see Type 2 diabetes in adults and Type 1 diabetes.
Wound debridement
Debridement of slough, necrotic tissue, and surrounding callus of the ulcer is recommended, after taking account of relative contraindications such as pain or severe ischemia.[22][62] The goal of debridement is to create a clean wound bed and promote wound healing.
Sharp debridement of ulcers using surgical instruments remains the standard of care, despite a lack of high-quality clinical trials to support its use. [
]
Numerous alternative debridement techniques exist, including using enzymes, larvae, hydrogels, lasers and ultrasound; however there is currently insufficient evidence to support the routine use of any of these over sharp debridement, according to the International Working Group on the Diabetic Foot (IWGDF).[62]
Wounds with tunneling (i.e., the presence of deep sinus tracts), copious exudate, or a significant amount of overlying eschar (i.e., dried/desiccated material) should be referred to an interdisciplinary foot clinic for debridement.[63] Surrounding callus should be debrided (usually by a podiatrist) to optimize offloading of the ulcer periphery and facilitate re-epithelialization.
Neuropathic ulcers can usually be debrided without the need for local anesthesia.[38]
There is reasonable-quality evidence that negative pressure wound therapy after surgical debridement may decrease the time to healing, and the IWGDF and the UK’s National Institute for Health and Care Excellence (NICE) both recommend its use in this circumstance.[8][62] This type of therapy is especially useful in wound preparation for skin grafts and flaps and assists in the closure of deep, large wounds, according to ADA guidelines.[22]
Wound dressing
Evidence is sparse to inform decisions about the best choice of wound dressing for diabetic foot ulcers. Dressings that maintain a moist environment, including nonadherent dressings covered with a layer of gauze or other absorptive material, are commonly used.
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[ ]
[64] Use of a sucrose octasulfate-impregnated wound dressing is supported by the IWGDF and NICE, after other modifiable factors such as infection have been treated; however the ADA does not specifically recommend this type of dressing.[62][65][66]
Split-thickness skin grafting is a helpful option for achieving wound healing in patients with a large epithelial defect that has a tissue bed with healthy granulation. The success rate for autologous skin grafting is high; however, its use over high-pressure areas (namely, the heel and the plantar forefoot overlying the metatarsal heads) may be limited.
[ ]
See Emerging treatments for further discussion of adjunctive treatments for nonhealing ulcers, including hyperbaric and topical oxygen therapy, skin substitutes and other types of dressing.
Offloading footwear and devices
Repetitive trauma sustained during ambulation is the most common cause of foot ulcers in patients with diabetes. All patients with diabetes should be encouraged to routinely wear appropriate footwear, even if they do not have any signs of active foot ulceration. See Screening and Prevention sections for more information.
For those with active ulceration, offloading the foot is essential to minimize or avoid this repetitive trauma, in order to achieve ulcer healing.[38]
Well-fitted athletic or walking shoes with customized pressure-relieving orthoses are recommended for people with increased plantar pressures, as demonstrated by plantar calluses. Individuals with deformities such as hammertoes or bunions may require specialized footwear such as extra-depth shoes. Those with even more significant deformities, such as in Charcot neuro-osteoarthropathy, may require custom-made footwear.[22] There are no data to support specialized orthotics in average-risk patients.[48]
In people with active ulceration, total contact casts and nonremovable cast-walkers are the most effective options for offloading footwear, although removable cast-walkers and modified footwear can be considered if frequent access to the wound is required, according to IWGDF guidelines.[30] Nonremovable devices are contraindicated when there is both mild infection and mild ischemia, or moderate infection or ischemia, or heavy exudate present.
The IWGDF also recommends the following:[30]
In a person with diabetes and a neuropathic plantar forefoot or midfoot ulcer, a nonremovable knee-high device should be used as the first choice of offloading treatment: either a total contact cast or nonremovable knee-high walker, with the choice depending on the resources available, technician skills, patient preferences, and the extent of any foot deformity present.
If a nonremovable knee-high device is not tolerated or is contraindicated, a removable knee-high or ankle-high device is recommended second-line, with the patient encouraged to wear the device during all weight-bearing activities.
For neuropathic plantar rearfoot ulcers, consider a nonremovable knee-high offloading device over a removable device.
For nonplantar foot ulcers, use a removable offloading device, footwear modifications, toe spacers, orthoses, or digital flexor tenotomy, depending on the type and location of the foot ulcer.
In any patient using a knee-high or ankle-high offloading device, consider adding a shoe lift on the contralateral limb to improve comfort and balance.
Dietary advice and supplements
Malnutrition, including sarcopenia, is very common in patients with diabetes and may impair wound healing. There is a clear correlation with nutritional status and healing, and as such, a balanced diet with adequate fluids, calories, proteins and nutrients is fundamental to the healing process.[54] Patients should be screened for risk of malnutrition, and if present, malnutrition should be addressed with dietary counseling and supplementation as needed. Discuss individual nutritional goals with patients who have, or are at risk of, malnutrition, ideally within the context of an interdisciplinary team, which may include professionals such as podiatrists, dietitians, surgeons, primary care physicians, dermatologists, wound care specialists etc.[54] Optimal glycemic control is essential.
Caloric needs are high when a diabetic foot ulcer is present. Use indirect calorimetry as the gold standard for identifying energy needs. If indirect calorimetry is unavailable, there are other formulas available that can provide a starting point.[54] As a general guide, offer most people at risk of nutritional deficiencies a minimum of 25-30 calories per kg body weight per day, 1.25 to 1.50 g of protein per kg body weight per day, and 1 ml/kcal/day of fluid intake. For people with a high body mass index, lower calorie intake while still meeting protein goals may be appropriate.[54] Give priority to nutrient dense foods. Oral nutrition supplements (ONS) can be taken between meals as needed to help provide additional protein and micronutrients. If a patient is unable to meet estimated nutrient, energy, protein, and hydration needs despite nutrition interventions, discuss with them the benefits and harms of enteral or parenteral feeding to provide additional or an alternative source of nutrition support.[54]
Vitamins and minerals are essential to the health of the body and should be included in all nutritional assessments and supplementation programs.[54]
Antibiotic therapy
Culturing a specimen from a diabetic foot infection allows selection of appropriate antibiotic therapy. For guidance on collecting samples for microbiologic culture, see Investigations.
Do not start antibiotics if there are no active signs or symptoms of infection, for example with the goal of reducing the risk of future infection, or to promote healing.[41]
Prompt initiation of an empiric antibiotic regimen is recommended when there are signs of infection: the choice of antibiotic should be based on the likely etiologic agents, local antibiotic policy, and/or the advice of a microbiologist. When choosing an antibiotic for people with a suspected diabetic wound infection, also take account of:[8][41]
The severity of the diabetic foot infection according to IWGDF/IDSA or WIfI classification (mild, moderate, or severe; see Criteria for more details)
The risk of developing complications
Previous microbiologic results (including previous multiresistant organisms)
Previous antibiotic use
Patient preferences
Mild infection:[41]
Treat with a suitable oral empiric antibiotic regimen. Gram-positive cocci (staphylococci and streptococci) are the most common pathogens in acute infections and narrow-spectrum therapy is appropriate.[53] Consult your local prescribing guidance.
Options recommended by the IWGDF and IDSA if there are no complicating features are a semisynthetic penicillinase-resistant penicillin (IWDGF/IDSA suggest cloxacillin, which is not available in the US; dicloxacillin would be a suitable alternative) or cephalexin. If the patient has allergy or intolerance, alternatives include, clindamycin, levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole, or doxycycline.
In patients with recent antibiotic exposure, amoxicillin/clavulanate, levofloxacin, moxifloxacin, or trimethoprim/sulfamethoxazole are recommended options.
If MRSA is suspected or confirmed, use linezolid, trimethoprim/sulfamethoxazole, clindamycin, levofloxacin, moxifloxacin, or doxycycline.
Most patients with mild infection can be treated in the community.
Moderate or severe infection:[41]
Should be promptly referred to an established interdisciplinary diabetic foot clinic for further management
Consider hospital admission if the patient has a moderate infection that is complex (e.g., wound penetrates to subcutaneous tissues, contains a foreign body, or has discoloration, necrosis or gangrene), associated with severe foot ischemia or metabolic or hemodynamic instability, or if outpatient management has failed or is inappropriate, for example, requiring intravenous therapy or frequent dressing changes
Severe infections are usually treated as an inpatient with parenteral, broad-spectrum, empirical antibiotics. Oral antibiotics should generally not be used for severe infections, except as follow-on (switch) after initial parenteral therapy
If no complicating features: amoxicillin/clavulanate, ampicillin/sulbactam, cefuroxime, cefotaxime, or ceftriaxone are recommended options
If MRSA is suspected or confirmed: add or substitute with vancomycin, teicoplanin, linezolid, daptomycin, trimethoprim/sulfamethoxazole, or doxycycline
In patients with recent antibiotic exposure: piperacillin/tazobactam, cefuroxime, cefotaxime, ceftriaxone, or ertapenem
Macerated ulcer or warm climate: consider piperacillin/tazobactam, meropenem, imipenem/cilastatin or ciprofloxacin
Ischemic limb/necrosis/gas forming: amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin/tazobactam, ertapenem, meropenem, imipenem/cilastatin, or one of cefuroxime, cefotaxime, or ceftriaxone plus clindamycin or metronidazole
If the patient has risk factors for extended-spectrum beta-lactamase drug resistance: ertapenem, meropenem, imipenem/cilastatin, ciprofloxacin, amikacin, or colistimethate
In temperate climates, do not empirically target antibiotic therapy against Pseudomonas aeruginosa. But do use empiric treatment of P aeruginosa if it has been isolated from cultures of the affected site within the previous few weeks, in a person with moderate or severe infection who resides in tropical/subtropical climates.[41]
The Food and Drug Administration (FDA) and the European Medicines Agency warn that fluoroquinolones are associated with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system.[67][68][69] They recommend that fluoroquinolones should not be used for mild-to-moderate infections unless other appropriate antibiotics for the specific infection cannot be used. In addition to these restrictions, the FDA has issued warnings about the increased risk of aortic dissection, significant hypoglycemia, and mental health adverse effects in patients taking fluoroquinolones.[70][71]
Definitive therapy should be based on culture results and clinical response to the empiric regimen. Therapy should be continued for 1 to 2 weeks for patients with a skin or soft tissue infection.[41] If the infection is improving but is extensive and is taking longer than expected to resolve, or if the patient has severe peripheral arterial disease, 3 to 4 weeks of antibiotic treatment may be appropriate.[41] Further diagnostic tests or alternative treatments may need to be considered if the infection has not resolved after 4 weeks.[41]
It is worth noting that because of the impaired immune response and abnormal arteriovenous shunting present in the neuropathic foot, clinical signs of infection in patients with diabetes may be more subtle than in patients without diabetes. As such, the threshold for referral to specialty units should be low.
Surgery
For pressure offloading in patients with active ulceration, where conservative measures have failed, the IWGDF advises surgery can be considered as follows (to be used in combination with an offloading device):[30]
Achilles tendon lengthening or metatarsal head resection for neuropathic plantar metatarsal head ulcers
Joint arthroplasty for neuropathic hallux ulcers
Metatarsal osteotomy for neuropathic plantar ulcers on metatarsal heads 2-5
Digital flexor tenotomy for neuropathic plantar or apex ulcers on digits 2-5, secondary to a flexible toe deformity
Digital flexor tenotomy for nonplantar foot ulcers (depending on its location)
A revascularization procedure should be considered for anyone with peripheral artery disease, a foot ulcer and clinical findings of ischemia (absent pulses, monophasic or absent pedal Doppler waveforms, ankle pressure <100 mmHg or toe pressure <60 mmHg), and for those with ulcers that do not improve within 4 weeks despite appropriate management.[10] Seek an urgent vascular opinion if there are signs of severe ischemia: ankle-brachial pressure index <0.4, ankle pressure <50mmHg, toe pressure <30mmHg or transcutaneous oxygen pressure <30mmHg.
Revascularization should aim to restore adequate arterial blood flow to at least one of the foot arteries. The main options for this type of procedure are endovascular (usually balloon angioplasty with or without stent placement), open (surgical bypass or endarterectomy), or hybrid (a combination of both). The choice of procedure should be based on the patient’s individual risks and preferences, limb threat severity, anatomic distribution of peripheral artery disease, and the availability of an autogenous vein for bypass.[10] In patients with infrapopliteal disease undergoing endovascular intervention by percutaneous transluminal angioplasty, addition of a stent probably increases rates of technical success of the procedure compared to no stenting, although the impact on complications, longer-term success rates and mortality is uncertain.
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Endovascular intervention appears to be as effective as bypass surgery for limb preservation (i.e., avoiding above-ankle amputation). Repeat endovascular intervention is required in 35% to 65% of patients to treat recurrent stenosis or occlusions occurring after angioplasty alone or to treat in-stent restenosis occurring after stent placement.[72] A study found that patients with chronic limb-threatening ischemia who had an adequate saphenous vein for surgical revascularization had a lower incidence of major adverse limb event or death when compared to those who underwent endovascular intervention. However, patients who lacked an adequate saphenous vein conduit had similar outcomes to those who underwent endovascular intervention.[73]
Seek an urgent surgical opinion in cases of severe infection, or moderate infection with extensive gangrene, necrotising infection, suspected deep abscess, compartment syndrome, or severe lower limb ischemia.[41] Prompt removal of infected and necrotic tissues (within 24-48 hours), including bone if there is osteomyelitis, in combination with antibiotics has been shown to improve wound healing rates and lower major amputation rates.[41]
Minor amputations (i.e., toe or partial foot resections) may be performed on areas with irreversible gangrene.
Major amputations are generally reserved for two situations:
Infection or gangrene that is so extensive that reconstruction either is not possible or will not preserve meaningful function in the affected limb
Patients who have very little or no function in the limb (excluding previous history of stroke or paralysis).
Management of cardiovascular risk factors and considerations for associated comorbidities
In addition to optimizing glycemic control, management of other risk factors and associated conditions is important for course and outcomes.
Chronic kidney disease
Renal function should be considered when selecting antibiotic therapy. Check your local drug information source.
End-stage renal disease and renal replacement therapy in patients with diabetes-related foot disease is associated with high rates of amputation and mortality.[74][75][76]
In patients receiving renal replacement therapy, feet should be protected during the hemodialysis session (e.g., offloading with protective boot).[77]
Cardiovascular disease and risk factors
Patients with diabetic foot ulcers are at increased risk of cardiovascular-related morbidity and mortality compared with patients with diabetes without foot ulcers.[78][79][80]
Control of blood pressure and lipid levels may reduce risk of vascular complications.[18] All patients should receive regular blood pressure and lipid monitoring along with lifestyle advice and optimal pharmacologic management.
Aggressive cardiovascular risk management (blood pressure, lipids, glycemic control) has been demonstrated to reduce mortality in patients with diabetic foot ulcers in one study.[81]
Note that overly aggressive antihypertensive treatment may result in reduced limb perfusion, increasing the risk of complications.[82]
Heart failure
Patients with diabetic foot ulcers have a higher prevalence of heart failure compared with patients with diabetes without foot ulcers, and the prevalence increases with increasing severity.[83]
Comorbid heart failure is associated with a worse prognosis, with lower healing rates, and increased risk of recurrence and amputations.[83]
Edema (associated with heart failure) may affect tissue perfusion and wound healing and should be treated where present.[38]
Depression
Depression and other mental health issues such as anxiety are common comorbidities in those with diabetes-related foot disease.[84]
Depression has been associated with a higher risk of developing diabetic foot ulcers and also a higher risk of major lower-limb amputation and mortality.[85][86][87][88]
Screening for depression is recommended.[82]
Follow-up and referral
Nonhealing foot ulcers and foot infections have the potential to progress suddenly, with few warning signs. The patient should be followed up every 1-2 weeks to assess for resolution of infection and check for wound healing. A wound that has not healed or decreased in area by ≥50% within 2-4 weeks should be referred to a diabetic foot clinic or inpatient unit. For chronic diabetic foot ulcers that have failed to heal with optimal standard care alone, adjunctive treatment may be considered in secondary care. There is a wide range of options, collectively referred to as "advanced wound therapy" by the ADA, including negative-pressure wound therapy, placental membranes, bioengineered skin substitutes, several acellular matrices, autologous fibrin and leukocyte platelet patches, and topical oxygen therapy.[22] See Emerging treatments for further discussion of these.
Primary care providers should provide basic clinical care at an initial visit for a new diabetic foot ulcer, but they should also have a low threshold to refer to interdisciplinary foot clinics or inpatient units for more focused care. Lack of recognition of ischemia and infection are two major, but avoidable, pitfalls that lead to delayed referral.[89] Interdisciplinary care - usually including at least a podiatrist and vascular surgeon with experience and interest in diabetes-related foot disease, perhaps with orthopedic, infectious disease, dermatologic, and prosthetist/orthotist input - has repeatedly been demonstrated to significantly lower leg amputation rates.[90][91][92][93]
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